ABSTRACT Treatment of knee cartilage defect, a true challenge, should not only reconstruct hyaline cartilage on a long-term basis, but also be able to prevent osteoarthritis. Osteochondral knee lesions occur in either traumatic lesions or in osteochondritis dissecans (OCD). These lesions can involve all the articular surfaces of the knee in its three compartments. In principle, this review article covers symptomatic ICRS grade C or D lesions, depth III and IV, excluding management of superficial lesions, asymptomatic lesions that are often discovered unexpectedly, and kissing lesions, which arise prior to or during osteoarthritis. For clarity sake, the international classifications used are reviewed, for both functional assessment (ICRS and functional IKDC for osteochondral fractures, Hughston for osteochondritis) and morphological lesion evaluations (the ICRS macroscopic evaluation for fractures, the Bedouelle or SOFCOT for osteochondritis, and MOCART for MRI). The therapeutic armamentarium to treat these lesions is vast, but accessibility varies greatly depending on the country and the legislation in effect. Many comparative studies have been conducted, but they are rarely of high scientific quality; the center effect is nearly constant because patients are often referred to certain centers for an expert opinion. The indications defined herein use algorithms that take into account the size of the cartilage defect and the patient's functional needs for cases of fracture and the vitality, stability, and size of the fragment for cases of osteochondritis dissecans. Fractures measuring less than 2 cm(2) are treated with either microfracturing or mosaic osteochondral grafting, between 2 and 4 cm(2) with microfractures covered with a membrane or a culture of second- or third-generation chondrocytes, and beyond this size, giant lesions are subject to an exceptional allografting procedure, harvesting from the posterior condyle, or chondrocyte culture on a 3D matrix to restore volume. Cases of stable osteochondritis dissecans with closed articular cartilage can be simply monitored or treated with perforation in cases of questionable vitality. Cases of open joint cartilage are treated with a PLUS fixation if their vitality is preserved; if not, they are treated comparably to osteochondral fractures, with the type of filling depending on the defect size.

[Show abstract][Hide abstract]ABSTRACT:
Purpose
Our purpose was to examine the Level I and II evidence for the use of osteochondral cylinder transfer technique (OCT) for cartilage repair.
Methods
A literature search was carried out for Level I and II evidence studies on cartilage repair using the PubMed database. All the studies that involved OCT were identified. Only Level I and II studies that compared OCT to other modalities of treatment such as microfracture (MF) and autologous chondrocyte implantation (ACI) were selected.
Results
A total of 8 studies matched the selection criteria with 2 Level I and 6 Level II studies. Four studies compared OCT with MF, 3 compared OCT with ACI, and one compared all 3 techniques. Of 3 studies, 4 came from a single center. Mean age of patients ranged from 24 to 33 years, and mean follow-up ranged from 9 to 124 months. The studies from the single center showed superior results from OCT over MF, especially in younger patients, with one study having long-term follow-up of 10 years. They also showed an earlier return to sports. The size of the lesions were small (average < 3 cm2). The 4 other independent studies did not show any difference between OCT and ACI, with one study showing inferior outcome in the OCT group. Magnetic resonance imaging (MRI) showed good osseous integration of the osteochondral plugs to the subchondral bone. Histologic examination showed that there was hyaline cartilage in the transplanted osteochondral plugs but no hyaline cartilage between the plugs.
Conclusions
From the studies of a single center, OCT had an advantage over MF in younger patients with small chondral lesions. Comparison of outcomes between OCT and ACI showed no significant difference in 2 studies and contrasting results in another 2 studies. There was insufficient evidence for long-term results for OCT.
Level of Evidence
Level II, systematic review of Level I and II studies.

[Show abstract][Hide abstract]ABSTRACT:
Osteochondral defects affect both the articular cartilage and the underlying subchondral bone, but poor osteochondral regeneration is still a daunting challenge. Although the tissue engineering technology provides a promising approach for osteochondral repair, an ideal biphasic scaffold is in high demand with regards to proper biomechanical strength. In this study, an oriented poly( L -lacticacid)- co -poly( ε -caprolactone) P(LLA-CL)/collagen type I(Col-I) nanofiber yarn mesh, fabricated by dynamic liquid electrospinning served as a skeleton for a freeze-dried Col-I/ Hhyaluronate (HA) chondral phase(SPONGE) to enhance the mechanical strength of the scaffold. In vitro results show that the Yarn Col-I/HA hybrid scaffold (Yarn-CH) can allow the cell infiltration like sponge scaffolds. Using porous beta-tricalcium phosphate (TCP) as the osseous phase, the Yarn-CH/TCP biphasic scaffold was then assembled by freeze drying. After combination of BMSCs, the biphasic complex was successfully used to repair the osteochondral defects in a rabbit model with greatly improved repairing scores and compressive modulus.

Journal of Biomedical Materials Research Part A 04/2014; DOI:10.1002/jbm.a.35206 · 2.83 Impact Factor

[Show abstract][Hide abstract]ABSTRACT:
Osteochondral autologous transplantation is frequently used to repair small cartilage defects. Incongruence between the osteochondral graft surface and the adjacent cartilage leads to changed friction and contact pressure. The present study wanted to analyze the differences between intact and surgically treated cartilage surface in respect to contact pressure and frictional characteristic (dissipated energy). Six ovine carpometacarpal joints were used in the present study. Dissipated energy during instrumentally controlled joint movement as well as static contact pressure were measured in different cartilage states (intact, defect, deep-, flush-, high-implanted osteochondral graft and cartilage failure simulation on a high-implanted graft). The best contact area restoration was observed after the flush implantation. However, the dissipated energy measurements did not reveal an advantage of the flush implantation compared to the defect and deep-implanted graft states. The high-implanted graft was associated with a significant increase of the mean contact pressure and decrease of the contact area but the dissipated energy was on the level of intact cartilage in contrast to other treatments where the dissipated energy was significantly higher as in the intact state. However the cartilage failure simulation on the high-implanted graft showed the highest increase of the dissipated energy.

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Treatment of knee cartilage defect in 2010 S141IntroductionCartilage tissue has mechanical properties that allow move-ment of the joint surfaces, by combining absorption ofstresses, low friction, and high resistance to wear. Despiteits mechanical performance, cartilage tissue lacks blood andnerve vessels: the cells are supplied by diffusion throughthe extracellular matrix. This all suggests that in a complexmechanical context, the low metabolic activity of cartilagetissue protects it from excessive physical stresses. How-ever, vascular paucity results in cartilaginous lesions havinga low spontaneous repair potential. Development of surgi-cal techniques is in full expansion with the major challengeof hyaline cartilage reconstruction on a bone base, the onlylong-lasting and viable solution for cartilage lesions. This isthe therapeutic challenge for the coming decades.Lesion assessmentThree factors are used to assess the initial cartilage lesion:the patient’s clinical status and the lesion’s size and type.The indication for management is based on the deteriora-tion of the functional status measured by pain and functionallimitation; these criteria are validated by a number of clin-ical scores [1]. The most frequently used functional scoresare the International Cartilage Repair Society (ICRS) score,the International Knee Documentation Committee (IKDC)functional score, and the Hughston score. The ICRS is avalidated score used to evaluate the repair of cartilagelesions, to evaluate the functional status (normal, nearlynormal, abnormal, and severely abnormal), to compare theinjured side with the healthy side (as a percentage of thehealthy side), to evaluate pain using an analogic pain scale,and to classify the sports level from normal to severelyabnormal [2]. The functional IKDC has not been specifi-cally validated for cartilage lesions, but it is a frequentlyused score. It evaluates, from 0 to 100, the level of activ-ity with no pain, stiffness, effusion, locking, the patient’ssports activities, and the knee’s optimal functioning. Thefunctional IKDC is completed by the physical IKDC, whichassesses intra-articular effusion, loss of range of motion,ligament laxity, joint cracking (crepitus), disease relatedto grafting sites, and hopping on one foot. It is also usedto analyze radiographic images. Each group of clinical andradiographic criteria is classified in grades: normal, nearlynormal, abnormal, and severely abnormal. A final grade isgiven to the patient corresponding to the lowest grade [3,4].The Hughston score is more specifically used by pediatricorthopaedic physicians and was designed to assess the treat-ment of osteochondritis lesions in children [5,6]. It classifiespatients into five clinical categories from failure to an excel-lent clinical result (Table 1).The lesion size can be measured in different ways. Thestandard radiological work-up can be used to estimate thewidth on the AP view of the knee and the length on thelateral knee image. However, the CT arthrogram, MRI, andarthro-MRI provide a more precise appreciation of the widthon AP slices and length on sagittal slices; this measurementmakes it possible to calculate the surfaces. Arthroscopydirectly measures the size of the lesion using either a probe,cylindrical gauges, or the measurement of the lesionalTable 1Hughston Score.Excellent4Normal sports activityNo functional symptomNormal clinical examinationNormal sports activityPain on intense activityNormal clinical examinationPain and hydrarthrosis if intenseactivitySport normalNormal clinical examinationPain and hydrarthrosis if moderateactivityLoss of flexion less than 20◦Cessation of sports activityPain and hydrarthrosis in dailyactivitiesLoss of flexion greater than 20◦Good3Fair2Poor1Failure0arc described by Robert. Directly visualizing the lesion,arthroscopy can appreciate the depth of the lesion usingthe ICRS grades:• grade 1: nearly normal (superficial lesions): softening, fib-rillations, lacerations, fissures;• grade 2: abnormal (less than 50% of cartilage depth);• grade 3: severely abnormal (cartilage defects extendingdown to more than 50% of cartilage depth);• grade 4: severely abnormal (lesion extending past sub-chondral plate, bone exposed).According to the ICRS guidelines, the seat of the lesionis represented by identifying the location of the cartilageinvolvement on drawings of the articular surfaces: a lateralview of the knee, an AP view in perspective of the femur, asuperiorviewofthetibiainperspective,andaninferiorviewof the patella in perspective. There are four specific radio-graphic classifications for osteochondritis lesions in children(OCD). Two locate the lesions on the AP and lateral imagesof the knee: the Cahill and Berg [7], (Fig. 1) and Harding [8],(Fig. 2) classifications. The two other classifications evalu-ate the radiological signs of OCD, classifying lesions into fourpathological stages: the Bedouelle [9] and Hughston et al.classifications [6].Bedouelle classification:• stage 1: clearly incomplete well-defined image (Ia) withmore or fewer calcifications within (Ib);• stage2:presenceofanodule(IIa)withmoreorlessshrink-age of the nodule in relation to the condyle (IIb);• stage 3: sleigh-bell aspect;• stage 4: free fragment in the joint with an empty with anempty bed.Hughston et al. classification:• stage 0: osteoarthritis, or impingement of the joint spacegreater than 50%;

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S142 G. Versier, F. DubranaFigure 1medial condyle (internal half). Zone 2: medial condyle (externalhalf). Zone 3: femoral notch. Zone 4: lateral condyle (internalhalf). Zone 5: lateral condyle (external half).Diagram: Cahill and Berg classification. Zone 1:• stage 1: condyle irregularities, impingement of the jointspace less than 50%;• stage 2: condyle flattening;• stage 3: healing zone with defect or sclerosis;• stage 4: normal radiographic image.The ICRS recommends MRI for the diagnosis and evalua-tion of cartilage lesion repairs, a noninvasive, reproducibleexam that, when done well, is precise and informative. Inthe literature, there is consensus on advising two sequencesthat are simple to perform: the fast spin-echo (FSE) T2-weighted sequence, which shows effusion, bone edema, andalteration of the cartilage surface, and the 3D GRE T1-weighted sequence, which reveals alterations in cartilagethickness and provides very precise information on the sub-chondral bone. These two sequences are used to determinethe lesion’s ICRS grade. To evaluate cartilage repair, theMOCART score [10,11] is used, which is based on nine cri-teria: filling at the edges (lateral integration), condition ofthe surface (lamina splendens), homogeneity of the struc-ture, type of signal on the FSE T2-weigted sequence, typeof signal on the 3D GRE FS sequence, presence of a subchon-dral radiolucent line, examination of the subchondral bone,presence of adherences and visualization of effusion.Current therapeutic methodsThe therapeutic tools aim to fill the cartilage loss so asto restore joint congruence, if possible to induce hya-line healing and thus prevent long-term osteoarthriticdegeneration. They can be classified into subchondral stim-ulation repair methods, most frequently resulting in aFigure 2the Blumensaat line. Zone B: between zone A and C. Zone C:behind the tangential line to the posterior cortex of the femoraldiaphysis.Diagram: Harding classification. Zone A: in front offibrous scar (microfracturing, Pridie drilling, and abrasion),reconstruction methods contributing mature cartilage tothe osteochondral unit (mosaicplasty and osteochondralallografting for massive chondral defects), and regenera-tion through grafting autologous chondrocyte cells aimingfor hyaline repair. Nevertheless, the follow-up biopsiesare often disappointing, with hyaline cartilage frequentlyabsent even in very costly regeneration using cell cultureimplantation techniques.MicrofracturingMicrofracturing is a reference repair technique to which theinternational literature compares all emerging techniques.Initially described by Richard Steadman et al. [12] and firstreported in 1997 [13], microfracturing should not be con-fused with Pridie drilling with a motorized drill and bit,even if this technique is widely used in France with identicalhistological and tissue objectives.The principle of this technique is to obtain healing of thecartilage defect with mesenchymal stem cells contained insubchondral bone that will colonize a fibrous clot favoringcreation of substitution cartilage. The technique initiallydescribed by Steadman et al. [13] consisted in débride-ment of the lesion’s edges, delicate ablation of the calcifiedplaque, or ‘‘tidemark,’’ and then drilling microfractures tothe vascularized subchondral area. These microfractures aremade with a thin square nail or, better yet, with angulatedpunches every 3—4mm and 3—4mm deep. Bleeding shouldbe present, clearly visible without or upon removing thetourniquet (Fig. 3). This bleeding will induce the creation of

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Treatment of knee cartilage defect in 2010S143Figure 3Microfractures with bleeding control.a superclot, colonized by multipotent stem cells, platelets,and growth factors. After multiplication and dedifferenti-ation of the mesenchymal cells in this clot, a substitutionfilling tissue appears, which is for the most part fibrocar-tilaginous with type I collagen. Naturally, the properties ofthe fibrocartilage are different, inevitably leading to dete-rioration and raising the question of maintaining the resultsover the long term.Even though the microfracturing technique has neverbeen assessed in France, a survey on practices con-ducted by the French Arthroscopy Society (Société Franc ¸aised’Arthroscopie) showed that microfracturing is only usedby one-third of the surgeons who treat cartilage lesions,the majority preferring mosaicplasty and the Pridie drillingtechnique.In the literature, four level 1 studies [14—17] showedthat the results of microfracturing are quite good, compa-rable to chondrocyte culture grafting, less effective thanmosaicplasty. However, the follow-up period in these stud-ies was short. A recent powerful meta-analysis carried outby Mithoefler et al. [18] combined 28 studies with a total of3122 patients with a mean follow-up of 41months. It con-cluded that microfracturing gives good early results for goodfilling of cartilage defects but with fibrous tissue, explainingthe secondary deterioration beginning at 2years of follow-up. This regression is even more frequent in that the studyreporting these microfracturing results has a high level ofevidence and that the patients studied were very active.This technique seems to have a negative influence on sec-ondary chondrocyte culture for cases of failure, contrary togenerally accepted notions.In conclusion, this technique currently used in all of therandomized comparative studies, except in France, is sim-ple, can be done with arthroscopy throughout the knee, iseconomical, and provides good initial results. Since it pro-duces fibrocartilage, the results deteriorate over time. Itis particularly indicated for patients with a low functionaldemand and for lesions discovered accidentally that mea-sure less than 4cm2.PLUS microfracturingThis is a more recent technique whose principle ismicrofracturing covered by a protective membrane (perios-teum or synthetic matrix). Based on the research of Breinanet al. [19,20], Behrens et al. [21], and Jakob since 2003have developed the AMIC (autologous matrix-inducedchondrogenesis)microfracture with a collagen (I/III) membrane: theChondro-Gide®(Fig. 4A, B). The matrix can be glued in thecartilage loss area with biological glue, with the porous sideof the matrix remaining in contact with the bone surfaceor sutured with resorbable sutures like first-generationchondrocyte cultures. As shown by Dickhut et al., thematrix allows chondrogenic differentiation of human stemcells in vitro [22] but also the deposit of proteoglycans.This technique has a number of advantages: a procedureperformed in a single intervention, low risk of hemarthrosis,protection and stabilization of the fibrous clot, absence of adonor site, and a moderate price (the price of the matrix),with no costly cell culture. Deep osteochondritis-typelesions are treated with a complement to AMIC based ona grafting technique of cancellous bone enriched withplatelet-rich plasma [23]. Gille et al. [24] and Pascarellaet al. [25] have reported the results of their experience,showing significant improvement in function in level 4studies. In a series of 19 cases with a mean follow-up of24months, Pascarella et al. obtained 78% satisfied patientswith an IKDC score improving from 30 to 83. Gille andBehrens reported a series of 32 lesions in 26 patients witha mean 36months of follow-up: 87% of the patients seenagain were satisfied, but the ICRS decreased with time,going from 31 to 59 at 12months, 68 at 24months, 54at 36months, and 37 at 48months, a regression similarto simple microfracturing, even though this decrease inthe score was not statistically significant. Benthien andBehrens [26] reported on its advantages in the treatment ofpatellar lesions. A recently reported small series studied bytechniqueconsistingofcoveringaFigure 4brane. B. PLUS microfractures with membrane in place.A. PLUS microfractures before placing the mem-

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S144G. Versier, F. DubranaVerdonk’s team [27] challenges the value of this techniquebecause of the absence of signs of repair on MRI andparticularly the early appearance of osteophytes in threecases out of five, despite early favorable clinical results.3D acellular scaffoldsThree-dimensional scaffolding is an acellular filling sub-stitute made up of multilayered biomimetics (Fig. 5;MaioRegen®) alternating layers of type I collagen and layersof collagen and calcium hydroxyapatite in variable propor-tions. This technique, used notably at the Rizzoli Institute[28], has the major advantages of filling osteochondral losswith matrix while forgoing autologous chondrocyte culture,all within a single operation. Different cellular recruitmentexists at each layer of this matrix placed on a freshenedand bleeding background. The preliminary results of thisnew and simple method [28] are encouraging at the veryshort follow-up time of 6months, showing stability andthen resorption of the implant and complete filling of thedefect both macroscopically and with MRI, as well as func-tional improvement. Histologically, no ossification has beenobserved; however, a mixed tissue is maturing. Clinical,morphological, and histological assessment is therefore nec-essary over a longer time span.MosaicplastyThis technique was created and then developed further byLaszlo Hangody based on an animal study on the horse begunin1992.Thiswidespreadtechnique,thereferenceinFrance,has been the subject of two multicenter studies among theSFA members detailing the indications and the results at themedium term.This demanding technique consists in a transfer of ananatomic and functional osteochondral unit harvested onthe knee presenting an osteochondral lesion in a singleopen operation or under arthroscopy (Fig. 6A and B). Thegraft made is comparable on the macroscopic level to layingcobblestones, allowing the surgeon to obtain bone integra-tion, the presence of hyaline cartilage on the pegs, but afibrous cartilage interface. Over the short term, the mosaicgraft is a validated cartilage restoration technique [29]. Dif-ferent studies have taken an interest in the harvest site.In 2005, Garretson et al. demonstrated that the optimaland less restrictive site was the edges of the superomedialtrochlea. As for the size and number of pegs, in a teachingFigure 6A. Open mosaicplasty. B. Arthroscopic mosaicplasty.session Robert [30] detailed the respective advantages ofsmall and large pegs. The large pegs provide greater sta-bility, less substantial fibrous interpositions, and a greatercartilage surface, at the cost of more difficult filling incases needing multiple pegs and of probable greater mor-bidity with harvesting. Sgaglione [31] recommends 6- to8-mm-wide pegs between 15 and 20mm long. With time, atendency to use increasingly large pegs has been observed.This harvesting comes with a certain morbidity, estimatedat 0—36% in the literature [32,33]. Following harvesting ona healthy knee for talar lesions, Reddy et al. [32] reportedfour painful knees out of 11 at 4years of follow-up. On theother hand, Iwasaki et al. [33,34] reported no complicationsof harvesting for humeral lesions at 2years of follow-up.In a heterogeneous retrospective study on more than 1000mosaic grafts, Hangody et al. [35] reported 3% morbiditywith four infections and 36 cases of hemarthrosis. They alsoevaluated the role played by the location of the lesion,finding a positive influence of medial condylar lesions with92% good and very good results compared to 87% for lateralcondylar lesions and 79% for patellofemoral lesions.The utility of MRI assessment is recognized by all, par-ticularly when using ICRS sequences and the MOCART score.At 9years of follow-up, Tetta et al. [36] studied 24 patientstreated with mosaicplasty, with complete integration of thegraft in 75% of the cases, correlated with the MOCART score.From the point of view of the overall result, the goodand very good results reported in the literature range from72 to 92% at more than 8years of follow-up. The factors forthe best prognosis are usually found for lesions located onthe medial condyle, osteochondritis desiccans, deep, smalllesions, and the shortest time to surgery possible. Largelesions have the least favorable prognosis. No correlationhas been found between the size of the harvested tissueFigure 5Maioregen®3D multilayer matrix.

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Treatment of knee cartilage defect in 2010S145Figure 7Mega-OATS®.and the development of patellofemoral osteoarthritis, oftenat its beginnings and only radiologically visible: 13% at amean follow-up of 8years for the SFA and 3% for Hang-ody et al. [35]. Mosaic grafting therefore seems to be areliable technique at the short and long term. Much lessexpensive than the regenerative techniques, performed ina single surgical step, and providing immediate restorationof the cartilaginous surface while treating the entire osteo-chondral unit, mosaicplasty nevertheless remains a difficult,demandingtechniquenotwithoutcomplications.Thelimita-tion of the technique matches the size of the lesion to treat.The choice indication is a deep and small (less than 2cm2)lesion located on the medial condyle. Beyond 2cm2, Imhoff’steam [37,38] has used 20- or 35-mm-diameter autologousgrafting performed at the expense of the homolateral poste-rior condyle using the Méga OATS®ancillary instrumentation(Fig. 7). The largest series reported 33 cases operated forcondylar lesions that were a mean 6.2cm2reviewed with amean follow-up of 66months. Thirty-one of the 33 patientshad significantly improved and were willing to undergo theoperation again.Osteochondral grafting for massive chondraldefectsThe first use of osteochondral grafting for massive chon-dral defects dates from Lexer’s work in 1908. The techniqueconsists in using a fresh or frozen epiphyseal osteochondralallograft placed in an area of voluminous osteochondral lossprepared by drilling. The graft can be positioned with press-fit technology or fixed with buried screw fixation (Fig. 8).This technique is reserved for substantial cartilage loss,usually more than 4cm2, a truly salvage treatment. Sev-eral series have reported satisfactory results in more than75% of cases with a mean follow-up of 10years [39—41].These results seem less good with longer follow-up peri-ods, decreasing from 95% for 5years of follow-up to 66%at 20years of follow-up [42,43]. Screw fixation seems togive better results (94% good results), improving bone fix-ation [44]. Jamali et al. [45] reported less satisfactoryresults on the knee with the appearance of signs of earlypatellofemoral osteoarthritis in half the cases. On the tibia,a series of post-traumatic lesions of the tibial plateaureported favorable results in 67% over the long term, compa-rable to femoral allografts, with failures appearing duringarthroplasty. Preoperative joint impingement is a poor prog-nostic factor, as is allografting on kissing lesions [40].Nonetheless, since this technique has rarely been used,no level 1 or 2 study can be found in the literature. Thoseavailable are retrospective studies with expert opinion. Thistechnique requires a certified tissue bank and the cost ishigh. Yet recuperation of posterior condyle in bone bankscould facilitate the dissemination of this technique.Autologous chondrocyte culture graftingFirst-generation graftsWidely developed, used and disseminated by Lars Peter-son and Matts Brittberg’s [46] Swedish school and thenby Tom Minas, the principle involves placing within thetrimmed and bloodless defect a culture of autologous chon-drocytes that have undergone in vitro multiplication in thelaboratory, implanted under a patch of periosteum har-vested locally from the tibia and sutured to the edges ofthe cartilage loss before impermeabilization with biologi-cal glue (Fig. 9). Cell multiplication and maturation shouldoccur and fill the defect with hyaline cartilage. This is anexpensive technique, whose results remain controversial, inparticular in comparative studies with mosaicplasty [47] andeven microfracturing by Knutsen et al. [16]. Results havebeen published by a number of authors, including Brittbergand Peterson, who published the long-term results of thistechnique [48,49]; the histological results were not alwaysconsistent [15,47]. The results are reported for the mostpart on Swedish series in which the early follow-up includesfew patients lost to follow-up. Biopsies were performedwith confirmation of the hyaline-like phenotype. MicheliFigure 8Condylar osteochondral allograft.

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S146G. Versier, F. DubranaFigure 9Cell culture of chondrocytes with periosteal patch.et al. [50] reported a series of 50 patients with a minimumfollow-up of 36months, noting that a 5-point increase in themodified Cincinnati score; 84% of the patients had increasedfunction, 2% remained the same, and 13% declared that theirfunction had deteriorated. Peterson et al. [51] publishedtheir results on 94 patients with follow-up between 2 and9years. The results varied depending on the location of thedefects: for the patella, the results were good in 62% of thecases and increased to 85% if medialization of the anteriortibial tuberosity was associated. For the condylar lesions,92% good results have been announced. Condylar osteochon-dritis seems a good indication since the results were goodin 16 out of 18 patients. Biopsies show hyaline-like tissuewith type II collagen in immunohistochemistry. In 10—15% ofthe cases, biopsies showed an exaggerated response. At themedium term, Peterson et al. [51] reported a series of 61patients with a mean follow-up of 7.4years. The good resultswere stable over time: 81% at 2years and 83% between 5 and11years of follow-up. The failure rate was 16% and appearedin the first 2 years. Cole and Lee [52] reported a series of103 cases of cartilage loss in 83 patients evaluated with theCincinnati, IKDC, Tegner, Lysholm, and SF-12 scores. All thescores improved significantly in 30 patients with a minimumfollow-up of 2years; 79.3% of the patients declared they hadimproved.Recently, Peterson et al. [53] reported the long-termresults of the first 341 cases in a level 4 study (retrospec-tive study with one-third lost to follow-up), with a meanfollow-up of 12.8years and for lesions that measured amean 5.3cm2in size. Seventy-four percent of the patientscontinued to improve beyond the 10th year and 92% weresatisfied and willing to undergo the same operation if nec-essary. Although the initial presence of a kissing lesionworsened the long-term results, meniscectomy, age at thetime of surgery, and the lesion size did not influence theresultsatthelongestfollow-up.Fromandmedical-economicperspective, autologous chondrocyte cultures are muchcostlier than prostheses, and for the moment the benefitin terms of osteoarthritis prevention remains uncertain. Anumber of comparative studies of simple and inexpensiverepair techniques such as microfracturing [16] and mosaic-plasty [15,54—56] have not demonstrated the superiorityof cellular cultures. Only Bentley et al. [56] found thatfirst-generation chondrocyte grafting was better. This studyexamined more voluminous lesions up to 12.2cm2and themosaic grafting technique used small-diameter samples.Second-generation graftingTo prevent the problems related to the periosteum patch(ossification, detachment, calcifications, leakage), matriceshave been developed serving as artificial membranes. Thesematrices can be synthetic (carbone, polylactic or polygly-colic acid, or dacrylen), proteic (collagen, fibrin, gelatin), orpolysaccharid (alginate, agarose, hyaluronic acid). Particu-larly advantageous, hyaluronic acid, an extracellular matrixhomeostasis drug, acts by its interaction with CD44 and I-CAM 1. It also fights against chondrocyte apoptosis, oxidativestress, inhibits the catabolic interleukin IL-1 according toFukuda, and produces metalloproteases according to Juvoli.Its chondrogenic effect occurs in stimulating differentiation,regulating the matrix structure during chondrogenesis, andinfluencing cellular mobility, differentiation, and develop-ment.As early as 2002, Saris et al. [57] developed the cultureof chondrocytes selected for the presence of markers ofpreservation of the phenotypic characteristics requiredfor differentiation and maturation to obtain hyalin car-tilage [58], a culture that is injected on a membrane(Chondroselect®)duringsurgery.Thiscelltherapycanestab-lish a ‘‘chondrogenic potential score’’ for the cultureimplanted. In a highly rigorous level 1 study comparing 57cases undergoing this technique (Fig. 10) with 61 patientstreated with microfracturing, Saris showed a significant dif-ference in favor of chondrocyte implantation at 3years offollow-up, both clinically using both the Knee injury andFigure 10ACI).Chondrocelect®technique (second-generation

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Treatment of knee cartilage defect in 2010S147Osteoarthritis Outcome Score (KOOS) and the MOCART scoreon MRI, with 83% good results versus 62%. The best resultswereobservedforlesionstreatedearlyandwhenthecultureimplanted had a better ‘‘chondrogenic potential score,’’which argues in favor of continuing the research in this tech-nique of improving cell therapy.Third-generation chondrocyte graftingThese more recent techniques are still being evaluated.Their principle is culturing chondrocytes in an implantablebiological matrix with ideal properties: biocompatible,biodegradable, and bioactive while preserving the pheno-typic characteristics, thus favoring the cellular proliferationand synthesis of the extracellular matrix, which is perme-able, easy to use, and inexpensive. Here again hyaluronicacid is often used. Beginning in 2002, Marcacci et al. [59]developed a chondrocyte culture termed ‘‘third genera-tion,’’ on a matrix of esterified hyaluronic acid, HyalograftC®; this matrix can be superimposed in several layersusing a so-called mushroom technique (Fig. 11), thus fillingdeep cartilage loss in several thicknesses. This techniqueis also currently used by Brittberg. This procedure hasthree phases: first arthroscopic with débridement andchondrocyte harvesting, second classical cell culturing forapproximately 3weeks in presence of the matrix to obtainat least 4 million chondrocytes/cm2in presence of growthfactors (TGF, BMP, IGF) and stabilizers; and third, surgery(patella) or arthroscopy (tibia, femur) for débridement,placing biological glue, and 3D cell implantation, possi-bly stacking several layers. Preliminary results have beenreported by the precursors [60,61]. Clinical evaluation hasreported no level 1 or 2 studies to date, and one level 3 non-randomized prospective study [28] with, at a mean 5yearsof follow-up, a significant improvement in clinical scores,with a functional IKDC score improving from 39 to 80, andan MRI evaluation using the MOCART score showing inte-gration of the graft in 60% of the cases. Nevertheless, theseries of patients was very inhomogeneous, with half of thissmall series originating from relevant associated ligamentor meniscus repair. From a histological perspective, 55% ofthe biopsies found hyaline cartilage, 18% mixed cartilage,and 27% fibrocartilage. These results seem to be improvedover time with 83% hyaline cartilage beyond 18months [62],showing the need for a long-term study of this technique.Figure 11Brittberg mushroom technique.In a level 2 study, Zeifang et al. [63] found no significantdifference between first-generation chondrocyte graftingwith a periosteum patch and third-generation chondrocytegrafting in a matrix foundation, with certain clinical resultsat 2years of follow-up even favoring the oldest technique.In three-dimensional regenerationCartipatch®, from the TBF laboratory developed andassessed in France, seems to give results that are compara-ble with an algarose and alginate matrix (Fig. 12) during aphase II study (subjective IKDC score increasing from 36 to85 at 18months of follow-up), which needs to be confirmedin an upcoming prospective, randomized multicenter phaseIII study [64].methods,theSurgical indicationsThe ideal patient who may have the best result is a patientwho is less than 50years of age, for biological and cellularreasons, but also because of lower eligibility in terms of indi-cation for arthroplasty. The discomfort must be severe andresistant to well-conducted medical treatment. The kneemust be stable, with a favorable axis, i.e., unloading theFigure 12Culture with Cartipatch®culture.Figure 13ping.Aspect of a patellar cartilaginous lesion in T2 map-

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S148G. Versier, F. DubranaFigure 14condyle according to Imhoff.Mega-osteochondral graft sacrificing the posteriorlesion, with no morbid obesity (BMI<30). Smoking is unfa-vorable for bone healing and therefore unfavorable for deeplesions, but nothing in the literature proves that this holdstrue for cartilage, which is avascular. The lesion to treatmust be deep (ICRS grade 3 or 4) on a single surface, andkissing lesions should not be treated surgically. The lesion’ssize must be large enough, greater than 0.5cm2, withoutit being possible to define a maximum size, with occasion-ally indications for salvage surgery. We emphasize that inall cases this is not surgery for osteoarthritis. The absolutecontraindications that have been recognized are obesity,joint impingement, and inflammatory diseases; others arerelative because they can be dealt with at the same time,particularly for procedures in a single operation (microfrac-turing and mosaicplasty) or before cartilage treatment:ligament laxity stemming from ligament reconstruction, axisdefect to be treated with osteotomy and weight loss. Manyauthors advocate nearly systematic realignment osteotomy.Previous meniscectomy does not compromise the result.However, early treatment should be pursued. Beyond clini-cal evaluation, MRI is now the reference examination withICRS sequences (2D or 3D FSE T2 FS and 3D GRE T1 FS),which allow calculation of the MOCART score. In the future,T2 mapping (Fig. 13), which analyzes the deterioration ofcollagen fibers, will allow routine, more precise cartilageassessment. Arthroscopy can be part of the workup, notablyif chondrocyte grafting is planned.The available armamentarium is rich, but is not accessi-ble to everyone, particularly in France where legislation is-2

Treatment of knee cartilage defect in 2010S149unfavorable to research. Palliative repair procedures usingsubchondral stimulation produce filling with fibrocartilageand are easy to perform under arthroscopic guidance. Prac-ticable in all the compartments of the knee, for lesionsmeasuring less than 4cm2, these procedures give good earlyresults, but they deteriorate over time. Several authorshave reported their unfavorable effect in cases of sec-ondary grafting, contrary to certain widely held beliefs.More recently, subchondral bone stimulation procedureshave been associated with covering with a membrane or a3D multilayer substitute, providing better filling and there-fore better results. These PLUS microfractures provide goodshort-term results, but require long-term assessment com-pared to the much more expensive cell culture techniques.Mosaicplasty is part of the reconstruction techniques, bring-ing mature cartilage to the osteochondral unit. This is ahighly demanding technique that can be done with arthro-scopic guidance for a maximum of two or three pegs, orotherwise with arthrotomy. All authors agree to indicatethis procedure for lesions measuring at least 2cm2, partic-ularly for the condyles, providing 75—90% good and verygood results at medium and long terms, sometimes withproblems of hyaline cartilage integration. Autologous chon-drocyte culture grafting has greatly progressed in the past10years, evolving from culture under a periosteum patch tothird-generation matrices, particularly for solving the prob-lem of filling and immediate congruence. This technique isindicated for lesions that are larger than 2cm2. However,two sizeable problems persist: cost (equivalent to at lastfive TKA procedures) and particularly the need for in situalchemy, not yet sufficiently under control, but nonethelessindispensable to maturation. Although the clinical resultsare good and long-lasting, hyaline cartilage does not alwaysappear. This is where the importance of research in mul-tilayer molecular surfaces and cell selection in culturesbecomes all important.Finally, salvage procedures can turn to chondrocyteculture, but particularly to autografting procedures, an easybut expensive technique for the countries that have thisavailable. These allografts (Fig. 14) are reserved for cases ofsubstantial cartilage defect —greater than 4cm2— and givegood results, even though no prospective series has beenreported. Other than viral transmission, bone integrationremains a problem. The therapeutic choice should take sev-eral factors into account: the type of lesion (OCD or chondralfracture), location, size, depth, patient age, desired level ofactivity, morphotype, and finally the armamentarium avail-able.Overall, for cases of osteochondritis (Fig. 15), we followthe SoFCOT recommendations. When the joint cartilage isclosed (SoFCOT stage I), perforation in cases of question-able vitality of the nodule on MRI will give greater certaintyand satisfaction compared to screw fixation (Fig. 16). Ifthe cartilage is open (stage II), the lesion is unstable, andthe PLUS fixation proposed by Bernard Moyen, will providea good success rate, associating revascularization throughfreshening of the bed and possibly mixed fixation as per-formed by Beaufils (Fig. 17). When the bed is empty (stageIII), simple ablation of the free loose body (LB) outside thenonloadbearing areas should be abandoned; this incongru-ence (Fig. 18) will lead to early osteoarthritis. Filling shouldbe preferred, with the choice depending on the size of theFigure 16dritis dissecans.Arthroscopic screw fixation in a case of osteochon-Figure 17cans.PLUS fixation in a case of osteochondritis disse-bed. Under 2cm2, mosaicplasty gives reliable results, par-ticularly if the pegs are supported by an interpeg graft:between 2 and 4cm2, third-generation chondrocyte graftingis the best choice, and beyond this condylar mega-OATS®orallografting.Figure 18Empty osteochondritis cavity.

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S150G. Versier, F. Dubrana-2

Func?onal demand Mosaicplasty with arthroscopy PLUS Microfracturing CCA / 3D matrix CCA or Allogra?ing or megaOATS+ + –Func?onal demand Func?onal demand Open mosaicplasty +–Microfracturing –Func?onal demand +– PLUS microfracturing < 1 cm² 1–2 cm²2–4 cm²> 4 cm²Adult OC fracture ICRS 3 or 4, ICRS grade 3 or 4 Figure 19Decision tree for knee osteochondral fractures.For osteochondral fractures (Fig. 19), the decision willdepend on the size and the patient’s activity. Mosaicplastyis a choice treatment for lesions less than 2cm2, and in thefuture, depending on the results, PLUS microfracturing mayoccupy an important place. Larger lesions are the domainof chondrocyte grafting. Finally, lesions greater than 4cm2will be treated with either chondrocyte grafting or allo-graft, or mega-OATS®, with results that have not undergoneas extensive scientific assessment, therefore making themless reliable. As for the choice according to the patient’sactivity level, the current trend is to propose regenerationtechniques to young and active patients and other repair orreconstruction techniques to less active patients.Tibial lesions are rare. Small (less than 1cm2) lesionsaccessible with the alignment guide Fig. 20) are treatedwith retrograde mosaicplasty, which according to Hang-ody provides 87% good results. Larger tibial lesions arepreferentially treated with microfracturing, matrix, or 3Dchondrocyte culture, but here also there has not yet beensufficient follow-up and numbers of patients for reliableresults.In 2010, trochlear-patellar lesions continue to have apoor prognosis (respectively 55% and 79% ICRS A and B in theSFA 2010 and Hangody series). Small lesions are treated witha few mosaicplasty pegs, with mediocre results: 55—75%good results [30,35]. If microfracturing is chosen here, theresults are comparable. Recent articles advocate nearlyFigure 20device in the middle of the tibial defect.Positioning the ligament reconstruction alignment